Atmospheric pressure ion source by interacting high velocity spray with a target

ABSTRACT

An ion source is disclosed comprising a nebulizer and a target. The nebulizer is arranged and adapted to emit, in use, a stream of analyte droplets which are caused to impact upon the target and to ionize analyte to form a plurality of analyte ions.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.14/113,151 filed Oct. 21, 2013, which is the National Stage ofInternational Application No. PCT/GB2012/050888, filed 20 Apr. 2012,which claims priority from and the benefit of U.S. Provisional PatentApplication Ser. No. 61/614,734 filed Mar. 23, 2012, United KingdomPatent Application No. 1204937.5 filed on Mar. 21, 2012, U.S.Provisional Patent Application Ser. No. 61/478,725 filed on 25 Apr. 2011and United Kingdom Patent Application No. 1106694.1 filed on 20 Apr.2011. The entire contents of these applications are incorporated hereinby reference.

BACKGROUND OF THE PRESENT INVENTION

The present invention relates to an ion source for a mass spectrometerand a method of ionising a sample. The preferred embodiment relates to amass spectrometer and a method of mass spectrometry.

Atmospheric Pressure Ionization (“API”) ion sources are commonly used toionize the liquid flow from HPLC or UPLC chromatography devices prior toanalyzing the resulting gas phase ions via a mass spectrometer. Twotechniques which are most commonly used comprise Electrospray Ionization(“ESI”) and Atmospheric Pressure Chemical Ionization (“APCI”). ESI isoptimal for moderate to high polarity analytes and APCI is optimal fornon-polar analytes. API ion sources that combine both of thesetechniques have been proposed and realized in designs thatsimultaneously combine ESI and APCI ionization using geometries thatensure that the electric fields generated by each technique are shieldedand are independent of one another. These so called “multimode” ionsources have the advantage of being able to ionize analyte mixturescontaining a wide range of polarities in a single chromatographic runwithout the need to switch between different ionization techniques. U.S.Pat. No. 7,034,291 discloses a ESI/APCI multimode ionization sourcecomprising an ESI ion source and a downstream corona needle and U.S.Pat. No. 7,411,186 discloses a multimode ESI/APCI ion source. The knownmultimode ion sources suffer from the problem of being mechanicallycomplex.

Other universal or multimode ionization sources have been proposed forinterfacing liquid chromatography to mass spectrometry. One such exampleis a Surface Activated Chemical Ionization (“SACI”) ion source whichdirects a vapour stream from a heated nebuliser probe towards a broadarea charged target plate which is situated close to the ion inletaperture of the mass spectrometer and 15-20 mm away from the end of thenebuliser. The spray point of the SACI ion source is within the heatednebuliser probe so that the typical distance between the spray point ofthe SACI ion source and the target plate is 70 mm. This geometry with arelatively large distance between the sprayer and the target produces adivergent spray with a dispersed reflected flow at the target whichgenerally results in lower sensitivities when compared to optimized ESIand APCI sources. U.S. Pat. No. 7,368,728 discloses a known SurfaceActivated Chemical Ionisation ion source.

It is also known to place a small target in the form of a bead at closeproximity to the nebulised spray point in impactor nebulisers which areused in atomic absorption spectroscopy. An impactor nebuliser is, forexample, disclosed in Anal. Chem. 1982, 54, 1411-1419. The knownimpactor nebuliser is not used to ionise a sample.

It is desired to provide an improved ion source for a mass spectrometer.

SUMMARY OF THE INVENTION

According to an aspect of the present invention there is provided an ionsource comprising:

one or more nebulisers and one or more targets;

wherein one or more nebulisers are arranged and adapted to emit, in use,a stream predominantly of droplets which are caused to impact upon theone or more targets and to ionise the droplets to form a plurality ofions.

The droplets preferably comprise analyte droplets and the plurality ofions preferably comprise analyte ions.

However, according to another embodiment the droplets may comprisereagent droplets and the plurality of ions may comprise reagent ions.

According to the preferred embodiment reagent ions which are created mayreact, interact with or transfer charge to neutral analyte molecules andcause the analyte molecules to become ionised. Reagent ions may also beused to enhance the formation of analyte ions.

According to an embodiment one or more tubes may be arranged and adaptedto supply one or more analyte or other gases to a region adjacent theone or more targets.

The reagent ions are preferably arranged so as to ionise the analyte gasto form a plurality of analyte ions.

An analyte liquid may be supplied to the one or more targets and may beionised to form a plurality of analyte ions and/or a reagent liquid maybe supplied to the one or more targets and may be ionised to formreagent ions which transfer charge to neutral analyte atoms or moleculesto form analyte ions and/or which enhance the formation of analyte ions.

The one or more targets preferably comprise one or more apertures andwherein the analyte liquid and/or reagent liquid is supplied directly tothe one or more targets and emerges from the one or more apertures.

According to an embodiment the one or more targets may be coated withone or more liquid, solid or gelatinous analytes and wherein the one ormore analytes are ionised to form a plurality of analyte ions.

The one or more targets may be formed from one or more analytes and theone or more analytes may be ionised to form a plurality of analyte ions.

According to the preferred embodiment the ion source comprises anAtmospheric Pressure Ionisation (“API”) ion source.

The one or more nebulisers are preferably arranged and adapted such thatthe majority of the mass or matter emitted by the one or more nebulisersis in the form of droplets not vapour.

Preferably, at least 50%, 55%, 60%, 65%, 70%, 75%, 10%, 85%, 90% or 95%of the mass or matter emitted by the one or more nebulisers is in theform of droplets.

The one or more nebulisers are preferably arranged and adapted to emit astream of droplets wherein the Sauter mean diameter (“SMD”, d32) of thedroplets is in a range: (i) <5 μm; (ii) 5-10 μm; (iii) 10-15 μm; (iv)15-20 μm; (v) 20-25 μm; or (vi) >25 μm.

The stream of droplets emitted from the one or more nebuliserspreferably forms a stream of secondary droplets after impacting the oneor more targets.

The stream of droplets and/or the stream of secondary dropletspreferably traverse a flow region with a Reynolds number (Re) in therange: (i) <2000; (ii) 2000-2500; (iii) 2500-3000; (iv) 3000-3500; (v)3500-4000; or (vi) >4000.

According to the preferred embodiment substantially at the point of thedroplets impacting the one or more targets the droplets have a Webernumber (We) selected from the group consisting of (i) <50; (ii) 50-100;(iii) 100-150; (iv) 150-200; (v) 200-250; (vi) 250-300; (vii) 300-350;(viii) 350-400; (ix) 400-450; (x) 450-500; (xi) 500-550; (xii) 550-600,(xiii) 600-650; (xiv) 650-700; (xv) 700-750; (xvi) 750-800; (xvii)800-850; (xviii) 850-900; (xix) 900-950; (xx) 950-1000; and (xxi) >1000.

According to the preferred embodiment substantially at the point of thedroplets impacting the one or more targets the droplets have a Stokesnumber (S_(k)) in the range: (i) 1-5; (ii) 5-10; (iii) 10-15; (iv)15-20; (v) 20-25; (vi) 25-30; (vii) 30-35; (viii) 35-40; (ix) 40-45; (x)45-50; and (xi) >50.

The mean axial impact velocity of the droplets upon the one or moretargets is preferably selected from the group consisting of: (i) <20m/s; (ii) 20-30 m/s; (iii) 30-40 m/s; (iv) 40-50 m/s; (v) 50-60 m/s;(vi) 60-70 m/s; (vii) 70-80 m/s; (viii) 80-90 m/s (ix) 90-100 m/s; (x)100-110 m/s; (xi) 110-120 m/s; (xii) 120-130 m/s; (xiii) 130-140 m/s;(xiv) 140-150 m/s; and (xv) >150 m/s.

The one or more targets are preferably arranged <20 mm, <19 mm, <18 mm,<17 mm, <16 mm, <15 mm, <14 mm, <13 mm, <12 mm, <11 mm, <10 mm, <9 mm,<8 mm, <7 mm, <6 mm, <5 mm, <4 mm, <3 mm or <2 mm from the exit of theone or more nebulisers.

The one or more nebulisers are preferably arranged and adapted tonebulise one or more eluents emitted by one or more devices over aperiod of time.

The one or more devices preferably comprise one or more liquidchromatography separation devices.

The one or more nebulisers are preferably arranged and adapted tonebulise one or more clients, wherein the one or more eluents have aliquid flow rate selected from the group consisting of <1 μL/min; (ii)1-10 μL/min; (iii) 10-50 μL/min; (iv) 50-100 μL/min; (v) 100-200 μL/min;(vi) 200-300 μL/min; (vii) 300-400 μL/min; (viii) 400-500 μL/min; (ix)500-600 μL/min; (x) 600-700 μL/min; (xi) 700-800 μL/min; (xii) 800-900μL/min; (xiii) 900-1000 μL/min; (xiv) 1000-1500 μL/min; (xv) 1500-2000μL/min; (xvi) 2000-2500 μL/min; and (xvii) >2500 μL/min.

The one or more nebulisers may according to a less preferred embodimentcomprise one or more rotating disc nebulisers.

The one or more nebulisers preferably comprise a first capillary tubehaving an exit which emits, in use, the stream of droplets.

The first capillary tube is preferably maintained, in use, at apotential: (i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv) −2to −1 kV; (v) −1000 to −900 V; (vi) −900 to −800 V; (vii) −800 to −700V; (viii) −700 to −600 V; (ix) −600 to −500 V; (x) −500 to −400 V; (xi)−400 to −300 V; (xii) −300 to −200 V; (xiii) −200 to −100 V; (xiv) −100to −90 V; (xv) −90 to −80 V; (xvi) −80 to −70 V; (xvii) −70 to −60 V;(xviii) −60 to −50 V; (xix) −50 to −40 V; (xx) −40 to −30 V; (xxi) −30to −20 V; (xxii) −20 to −10 V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv)10-20 V; (xxvi) 20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V; (xxix) 50-60V; (xxx) 60-70 V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V(xxxix) 100-200 V; (xxxv) 200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500V; (xxxviii) 500-600 V; (xxxix) 600-700 V; (xi) 700-800 V; (xli) 800-900V; (xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV; (xlv) 3-4 kV; and(xlvi) 4-5 kV.

The first capillary tube is preferably maintained, in use, at apotential of (i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv)−2 to −1 kV; (x) −1000 to −900 V; (vi) −900 to −800 V; (vii) −800 to−700 V; (viii) −700 to −600 V; (ix) −600 to −500 V; (x) −500 to −400 V;(xi) −400 to −300 V; (xii) −300 to −200 V; (xiii) −200 to −100 V; (xiv)−100 to −90 V; (xv) 90 to −80 V; (xvi) −80 to −70 V; (xvii) −70 to −60V; (xviii) −60 to −50 V; (xix) −50 to −40 V; (xx) 40 to −30 V; (xxi) −30to −20 V; (xxii) −20 to −10 V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv)10-20 V; (xxxi) 20-30 V; (xxvii) 30-40V; (xviii) 40-50 V; (xxix) 50-60V; (xxx) 60-70 V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V;(xxxiv) 100-200 V; (xxxv) 200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500V; (xxxviii) 500-600 V; (xxxix) 600-700 V; (xl) 700-800 V; (xli) 800-900V; (xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV; (xlv) 3-4 kV; and(xlvi) 4-5 kV; relative to the potential of an enclosure surrounding theion source and/or an ion inlet device which leads to a first vacuumstage of a mass spectrometer and/or the one or more targets.

According to an embodiment a wire may be located within the volumeenclosed by the first capillary tube wherein the wire is arranged andadapted to focus the stream of droplets.

According to the preferred embodiment:

(i) the first capillary tube is surrounded by a second capillary tubewhich is arranged and adapted to provide a stream of gas to the exit ofthe first capillary tube; or

(ii) a second capillary tube is arranged and adapted to provide a crossflow stream of gas to the exit of the first capillary tube.

The second capillary tube preferably surrounds the first capillary tubeand/or is either concentric or non-concentric with the first capillarytube.

The ends of the first and second capillary tubes are preferably either:(i) flush or parallel with each other; or (ii) protruded, recessed ornon-parallel relative to each other.

The exit of the first capillary tube preferably has a diameter D and thespray of droplets is preferably arranged to impact on an impact zone ofthe one or more targets.

The impact zone preferably has a maximum dimension of x and wherein theratio x/D is in the range <2, 2-5, 5-10, 10-15, 15-20, 20-25, 25-30,30-35, 35-40 or >40.

The impact zone preferably has an area selected from the groupconsisting of (i) <0.01 mm²; (ii) 0.01-0.10 mm²; (iii) 0.10-0.20 mm²;(iv) 0.20-0.30 mm²; (v) 0.30-0.40 mm²; (vi) 0.40-0.50 mm²; (vii)0.50-0.60 mm²; (viii) 0.60-0.70 mm²; (ix) 0.70-0.80 mm²; (x) 0.80-0.90mm²; (xi) 0.90-1.00 mm²; (xii) 1.00-1.10 mm²; (xiii) 1.10-1.20 mm²;(xiv) 1.20-1.30 mm²; (xv) 1.30-1.40 mm²; (xvi) 1.40-1.50 mm²; (xvii)1.50-1.60 mm²; (xviii) 1.60-1.70 mm²; (xix) 1.70-1.80 mm²; (xx)1.80-1.90 mm²; (xxi) 1.90-2.00 mm²; (xxii) 2.00-2.10 mm²; (xxiii)2.10-2.20 mm²; (xxiv) 2.20-2.30 mm²; (xxv) 2.30-2.40 mm²; (xxvi)2.40-2.50 mm²; (xxvii) 2.50-2.60 mm²; (xxviii) 2.60-2.70 mm²; (xxix)2.70-2.80 mm²; (xxx) 2.80-2.90 mm²; (xxxi) 2.90-3.00 mm²; (xxxii)3.00-3.10 mm²; (xxxiii) 3.10-3.20 mm²; (xxxiv) 3.20-3.30 mm²; (xxxv)3.30-3.40 mm²; (xxxvi) 3.40-3.50 mm²; (xxxvii) 3.50-3.60 mm²; (xxxviii)3.60-3.70 mm²; (xxxix) 3.70-3.80 mm²; (xl) 3.80-3.90 mm²; and (xli)3.90-4.00 mm².

The ion source preferably further comprises one or more heaters whichare arranged and adapted to supply one or more heated streams of gas tothe exit of the one or more nebulisers.

According to an embodiment:

(i) the one or more heaters surround the first capillary tube and arearranged and adapted to supply a heated stream of gas to the exit of thefirst capillary tube; and/or

(ii) the one or more heaters comprise one or more infra-red heaters;and/or

(iii) the one or more heaters comprise one or more combustion heaters.

The ion source may further comprise one or more heating devices arrangedand adapted to directly and/or indirectly heat the one or more targets.

The one or more heating devices may comprise one or more lasers arrangedand adapted to emit one or more laser beams which impinge upon the oneor more targets in order to heat the one or more targets.

According to an embodiment the one or more targets are maintained, inuse, at a potential: (i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2kV; (iv) −2 to −1 kV; (v) −1000 to −900 V; (vi) −900 to −800 V; (vii)−800 to −700 V; (viii) −700 to −600 V; (ix) −600 to −500 V; (x) −500 to−400 V; (xi) −400 to −300 V; (xii) −300 to −200 V; (xiii) −200 to −100V; (xiv) −100 to −90 V; (xv) −90 to −80 V; (xvi) −80 to −70 V; (xvii)−70 to −60 V; (xviii) −60 to −50 V; (xix) −50 to −40 V; (xx) −40 to −30V; (xxi) −30 to −20 V; (xxii) −20 to −10 V; (xxiii) −10 to 0V; (xxiv)0-10 V; (xxv) 10-20 V; (xxvi) 20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V;(xxix) 50-60 V; (xxx) 60-70 V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii)90-100 V; (xxxiv) 100-200 V; (xxxv) 200-300 V; (xxxvi) 300-400 V;(xxxvii) 400-500 V; (xxxviii) 500-600 V; (xxxix) 600-700 V; (xl) 700-800V; (xli) 800-900 V; (xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV;(xlv) 3-4 kV; and (xlvi) 4-5 kV.

According to an embodiment the one or more targets are maintained, inuse at a potential (i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV;(iv) −2 to −1 kV; (v) −1000 to −900 V; (vi) −900 to −800 V; (vii) −800to −700 V; (viii) −700 to −600 V; (ix) −600 to −500 V; (x) −500 to −400V; (xi) −400 to −300 V; (xii) −300 to −200 V; (xiii) −200 to −100 V;(xiv) −100 to −90 V; (xv) −90 to −80 V; (xvi) −80 to −70 V; (xvii) −70to −60 V; (xviii) −60 to −50 V; (xix) −50 to −40 V; (xx) −40 to −30 V;(xxi) −30 to −20 V; (xxii) −20 to −10 V; (xxiii) −10 to 0V (xxiv) 0-10V; (xxv) 10-20 V; (xxvi) 20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V;(xxix) 50-60 V; (xxx) 60-70 V, (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii)90-100 V; (xxxiv) 100-200 V; (xxxi) 200-300 V; (xxxvi) 300-400 V;(xxxvii) 400-500 V; (xxxviii) 500-600 V; (xxxix) 600-700 V; (xl) 700-800V; (xli) 800-900 V; (xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV;(xlv) 3-4 kV; and (xlvi) 4-5 kV; relative to the potential of anenclosure surrounding the ion source and/or an ion inlet device whichleads to a first vacuum stage of a mass spectrometer and/or the one ormore nebulisers.

According to a preferred embodiment in a mode of operation the one ormore targets are maintained at a positive potential and the dropletsimpacting upon the one or more targets form a plurality of positivelycharged ions.

According to another preferred embodiment in a mode of operation the oneor more targets are maintained at a negative potential and the dropletsimpacting upon the one or more targets form a plurality of negativelycharged ions.

The ion source may further comprise a device arranged and adapted toapply a sinusoidal or non-sinusoidal AC or RF voltage to the one or moretargets.

The one or more targets are preferably arranged or otherwise positionedso as to deflect the stream of droplets and/or the plurality of ionstowards an ion inlet device of a mass spectrometer.

The one or more targets are preferably positioned upstream of an ioninlet device of a mass spectrometer so that ions are deflected towardsthe direction of the ion inlet device.

The one or more targets may comprise a stainless steel target, a metal,gold, a non-metallic substance, a semiconductor, a metal or othersubstance with a carbide coating, an insulator or a ceramic.

The one or more targets may comprise a plurality of target elements sothat droplets from the one or more nebulisers cascade upon a pluralityof target elements and/or wherein the target is arranged to havemultiple impact points so that droplets are ionised by multiple glancingdeflections.

The one or more targets may be shaped or have an aerodynamic profile sothat gas flowing past the one or more targets is directed or deflectedtowards, parallel to, orthogonal to or away from an ion inlet device ofa mass spectrometer.

At least some or a majority of the plurality of ions may be arranged soas to become entrained, in use, in the gas flowing past the one or moretargets.

According to an embodiment in a mode of operation droplets from one ormore reference or calibrant nebulisers are directed onto the one or moretargets.

According to an embodiment in a mode of operation droplets from one ormore analyte nebulisers are directed onto the one or more targets.

According to another aspect of the present invention there is provided amass spectrometer comprising an ion source as described above.

The mass spectrometer preferably further comprises an ion inlet devicewhich leads to a first vacuum stage of the mass spectrometer.

The ion inlet device preferably comprises an ion orifice, an ion inletcone, an ion inlet capillary, an ion inlet heated capillary, an iontunnel, an ion mobility spectrometer or separator, a differential ionmobility spectrometer, a Field Asymmetric Ion Mobility Spectrometer(“FAIMS”) device or other ion

The one or more targets are preferably located at a first distance X₁ ina first direction from the ion inlet device and at a second distance Z₁in a second direction from the ion inlet device, wherein the seconddirection is orthogonal to the first direction and wherein:

(i) X₁ is selected from the group consisting of (i) 0-1 mm; (ii) 1-2 mm,(iii) 2-3 mm; (iv) 3-4 mm; (v) 4-5 mm; (vi) 5-6 mm; (vii) 6-7 mm; (viii)7-8 mm; (ix) 8-9 mm; (x) 9-10 mm; and (xi) >10 mm; and/or

(ii) Z₁ is selected from the group consisting of (1) 0-1 mm; (ii) 1-2mm; (iii) 2-3 mm; (iv) 3-4 mm; (v) 4-5 mm; (vi) 5-6 mm; (vii) 6-7 mm;(viii) 7-8 mm; (ix) 8-9 mm; (x) 9-10 mm; and (xi) >10 mm.

The one or more targets are preferably positioned so as to deflect thestream of droplets and/or the plurality of ions towards the ion inletdevice.

The one or more targets are preferably positioned upstream of the ioninlet device.

The one or more targets preferably comprise either: (i) one or morerods, or (ii) one or more pins having a taper cone.

The stream of droplets is preferably arranged to impact the one or morerods or the taper cone of the one or more pins either: (i) directly onthe centerline of the one or more rods or pins or (ii) on the side ofthe one or more rods or the taper cone of the one or more pins whichfaces towards or away from the ion inlet orifice.

The mass spectrometer may further comprise an enclosure enclosing theone or more nebulisers, the one or more targets and the ion inletdevice.

The mass spectrometer may further comprise one or more deflection orpusher electrodes, wherein in use one or more DC voltages or DC voltagepulses are applied to the one or more deflection or pusher electrodes inorder to deflect or urge ions towards an ion inlet device of the massspectrometer.

According to an aspect of the present invention there is provided amethod of ionising a sample comprising:

causing a stream predominantly of droplets to impact upon one or moretargets to ionise the droplets to form a plurality of analyte ions.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising a method of ionising ions asdescribed above.

According to an aspect of the present invention there is provided a massspectrometer comprising:

an ion source including:

a target; and

a nebuliser configured to emit, in use, a stream formed predominantly ofdroplets which are caused to impact upon the target and to ionise thedroplets to form a plurality of ions.

According to an aspect of the present invention there is provided an ionsource comprising:

a target; and

a nebuliser configured to emit, in use, a stream formed predominantly ofdroplets which are caused to impact upon the target and to ionise thedroplets to form a plurality of ions.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

ionising a sample by generating a stream predominantly formed ofdroplets and ionising the droplets to form a plurality of ions byimpacting the droplets upon one or more targets.

According to an aspect of the present invention there is provided amethod of ionising a sample comprising generating a stream predominantlyformed of droplets and ionising the droplets to form a plurality of ionsby impacting the droplets upon one or more targets.

According to an aspect of the present invention there is provided adesolvation device comprising:

one or more nebulisers and one or more targets;

wherein one or more nebulisers are arranged and adapted to emit, in use,a stream predominantly of droplets which are caused to impact upon saidone or more targets and to cause said droplets to form desolvated gasphase molecules and/or secondary droplets.

According to an aspect of the present invention there is provided amethod of desolvation comprising:

causing a stream predominantly of droplets to impact upon one or moretargets and to cause said droplets to form desolvated gas phasemolecules and/or secondary droplets.

It will be apparent that the present invention extends beyond an ionsource or method of ionising a sample to include apparatus and methodsfor at least partially desolvating or further desolvating a stream ofdroplets. The resulting gas phase molecules and/or secondary dropletsmay be subsequently ionised by a separate ion source.

According to an aspect of the present invention there is provided a massspectrometer comprising:

a nebuliser comprising a first capillary tube and having an exit whichemits, in use a stream of analyte droplets; and

a target arranged <10 mm from the exit of the nebuliser;

characterised in that the mass spectrometer further comprises:

a liquid chromatography separation device arranged and adapted to emitan eluent over a period of time; and

an ion source arranged and adapted to ionise the eluent, the ion sourcecomprising the nebuliser and wherein, in use, the stream of analytedroplets is caused to impact upon the target and to ionise the analyteto form a plurality of analyte ions.

By way of contrast, the target of a SACI ion source is placed downstreamof the ion inlet orifice of a mass spectrometer and ions are reflectedback towards the ion inlet orifice.

According to another aspect of the present invention there is provided amethod of mass spectrometry comprising:

providing a nebuliser comprising a first capillary tube and having anexit which emits a stream of analyte droplets; and

positioning a target <10 mm from the exit of the nebuliser;

characterised in that the method further comprises:

providing a liquid chromatography separation device which emits aneluent over a period of time; and

ionising the eluent by causing the stream of analyte droplets to impactupon the target and to ionise the analyte to form a plurality of analyteions.

As discussed above, the spray point of a SACI ion source is within theheated nebuliser probe so that the typical distance between the spraypoint and a target plate is around 70 mm. By way of contrast, with thepreferred impactor ion source the spray point is located at the tip ofthe inner capillary tube and the distance between the spray point andthe target may be <10 mm.

It will be understood by those skilled in the art that a SACI ion sourceemits a vapour stream and the impact velocity of the vapour upon thetarget is relatively low and is approximately 4 m/s. By way of contrast,the impactor ion source according to the preferred embodiment does notemit a vapour stream but instead emits a high density droplet stream.Furthermore, the impact velocity of the droplet stream upon the targetis relatively high and is approximately 100 m/s.

It will be apparent therefore that the ion source according to thepresent invention is quite distinct from known SACI ion sources.

According to a preferred embodiment a liquid stream is preferablyconverted into a nebulised spray via a concentric flow of high velocitygas without the aid of a high potential difference at the sprayer ornebuliser tip. A micro target with comparable dimensions or impact zoneto the droplet stream is preferably positioned in close proximity (e.g.<5 mm) to the sprayer tip to define an impact zone and to partiallydeflect the spray towards the ion inlet orifice of the massspectrometer. The resulting ions and charged droplets are sampled by thefirst vacuum stage of the mass spectrometer.

According to the preferred embodiment the target preferably comprises astainless steel target. However, other embodiments are contemplatedwherein the target may comprise other metallic substances (e.g. gold)and non-metallic substances. Embodiments are contemplated, for example,wherein the target comprises a semiconductor, a metal or other substancewith a carbide coating, an insulator or a ceramic.

According to another embodiment the target may comprise a plurality ofplates or target elements so that droplets from the nebuliser cascadeupon a plurality of target plates or target elements. According to thisembodiment there are preferably multiple impact points and droplets areionised by multiple glancing deflections.

From an API source perspective, the combination of a close-coupledimpactor which also serves as a charged ionization surface provides thebasis of a sensitive multimode ionization source. The spray tip andmicro target are preferably configured in close proximity with aglancing impact geometry which results in increased spray flux at thetarget and significantly less beam divergence or reflected dispersionwhen compared to a known broad area SACI ion source. The preferredembodiment therefore provides a high sensitivity API source.

The preferred embodiment comprises a multimode ion source whichadvantageously can ionize high and low polarity analytes at highefficiency without the need to switch hardware or tuning parameters.

The droplets which impact the one or more targets are preferablyuncharged.

It will be apparent that the ion source and method of ionising ionsaccording to the present invention is particularly advantageous comparedwith a known SACI ion source.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, byway of example only, and with reference to the accompanying drawings inwhich:

FIG. 1 shows an impactor spray API ion source according to a preferredembodiment of the present invention;

FIG. 2A shows a plan view of a target and a first vacuum stage of a massspectrometer according to a preferred embodiment of the presentinvention with the nebuliser omitted and FIG. 2B shows a side view ofthe nebuliser or sprayer tip, target and first vacuum stage of a massspectrometer according to a preferred embodiment of the presentinvention;

FIG. 3 shows a conventional APCI ion source with a corona discharge pin;

FIG. 4 shows the relative intensities of five test analytes measuredusing a conventional Electrospray on source, a conventional APCI ionsource and an impactor ion source according to the preferred embodiment;

FIG. 5 shows the effect of target potential on ion signal according to apreferred embodiment of the present invention;

FIG. 6A shows a mass spectrum obtained from an impactor spray ion sourceaccording to a preferred embodiment of the present invention with atarget potential of 2.2 kV, FIG. 6B shows a mass spectrum obtained froman impactor spray source according to an embodiment of the presentinvention with a target potential of 0V and FIG. 6C shows a massspectrum obtained with a conventional Electrospray ion source with anoptimized capillary potential of 4 kV;

FIG. 7 shows a known Surface Activated Chemical Ionisation ion source;

FIG. 8 shows a comparison of the relative intensities obtained with aconventional SACI ion source and an impactor ion source spray accordingto a preferred embodiment;

FIG. 9 shows data obtained from a Phase Doppler Anemometry analysis ofthe droplets emitted from a preferred nebuliser; and

FIG. 10 shows a comparison of the radial distribution of the data ratefor a pneumatic nebuliser according to an embodiment of the presentinvention and from a heated nebuliser such as used in a SACI ion source.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows a schematic of the general layout of an impactor spray APIion source according to an embodiment of the present invention. A flowof liquid containing analyte is arranged to enter a nebuliser or sprayer1 and is delivered to the sprayer tip 2 via a liquid capillary tube 3.The liquid capillary tube 3 is preferably surrounded by a secondcapillary 4 which preferably includes a gas inlet 5 to deliver a streamof high velocity gas to the exit of the liquid capillary tube 3.According to an embodiment the inner diameter of the liquid capillarytube 3 is 130 μm and the outer diameter of the liquid capillary tube 3is 270 μm. The inner diameter of the second (gas) capillary tube 4 ispreferably 330 μm. This arrangement produces a nebulised spray whichcontains droplets with a typical diameter of 10-20 μm and which havevelocities greater than 100 m/s at a close distance from the sprayertip.

The resulting droplets are preferably heated by an additional flow ofgas that enters a concentric heater 6 via a second gas inlet 7. Thenebuliser or sprayer 1 may be hinged to the right hand side of the ioninlet cone 8 of a mass spectrometer so that it can swing to vary thehorizontal distance between the sprayer tip and an ion inlet orifice 9.The probe may also configured such that the vertical distance betweenthe sprayer tip and the ion inlet orifice 9 can also be varied. A target10 which preferably has a similar dimension to that of the liquidcapillary tube 3 is placed between the sprayer tip and the ion inletorifice 9. The target 10 can preferably be manipulated in the x and ydirections (in the horizontal plane) via a micro adjuster stage and ispreferably held at a potential of 0-5 kV relative to a source enclosure11 and the ion inlet orifice 9. The ion inlet cone 8 is surrounded by ametal cone gas housing 12 that is preferably flushed with a low flow ofnitrogen gas that enters via a gas inlet 13. All gasses that enter thesource enclosure preferably leave via a source enclosure exhaust 14 orthe ion inlet orifice 9 which is pumped by the first vacuum stage 15 ofthe mass spectrometer.

FIG. 2A shows a schematic plan view of an embodiment of the presentinvention with the nebuliser or sprayer 1 omitted. A target 10 islocated adjacent the first vacuum stage 15 of the mass spectrometer.According to an embodiment the target 10 may comprise a 0.8 mm diameterstainless steel pin which preferably incorporates a straight tapersection over a distance of 5 mm. The pin is preferably positioned at ahorizontal distance X₁ of 5 mm from the ion inlet orifice 9. The pin 10is preferably positioned such that the point of impact between the probeaxis and the target 10 is on the side of the taper cone that faces theion inlet orifice 9 as shown in FIG. 2B. This position results in anoptimized glancing angle of incidence shown as an arrowed line 16 in theend view schematic of FIG. 2B, FIG. 2B also shows the relative verticalpositions of the nebuliser or probe 2 and target 10 according to thepreferred embodiment i.e. Z₁=9 mm and Z₂=1.5 mm. The nebuliser orsprayer 2 is preferably maintained at 0V, the target 10 is preferablyheld at 2.2 kV, the ion inlet cone is preferably held at 100 V, the conegas housing is preferably held at 100 V and the heater assembly andsource enclosure are preferably held at ground potential. The nitrogennebuliser gas is preferably pressurized to 7 bar, the nitrogen heatergas flow is preferably pressurized to deliver 1200 L/hr and the nitrogencone gas flow is preferably pressurized to deliver 150 L/hr.

A series of tests were conducted to test the relative sensitivities ofthe preferred impactor spray source, a conventional ESI ion source and aconventional APCI ion source.

The conventional ESI ion source was constructed by removing the target10 and applying a potential of 2.5 kV directly to the sprayer tip. Allother potentials and gas flows were maintained as above.

The APCI ion source was constructed by replacing the nebuliser orsprayer 2 with a conventional heated nebuliser probe 17 as shown in FIG.3 as used in commercial APCI ion sources and adding a corona dischargepin 18. The tip of the corona discharge pin 18 was located at a distanceX=7 mm and Z=5.5 mm as shown in FIG. 3. The APCI ion source probe wasoperated at 550° C., the heater gas was unheated at a flow rate of 500L/hr and the corona discharge pin 18 was set at a current of 5 μA. Allother settings were as described above.

A test solution was prepared consisting of 70/30 acetonitrile/water andcontaining sulphadimethoxine (10 pg/μL), verapamil (10 pg/μL),erythromycin (10 pg/μL), cholesterol (10 ng/μL) and cyclosporin (100pg/μL). The test solution was infused at a flow rate of 15 μL/min into acarrier liquid flow of 0.6 mL/min of 70/30 acetonitrile/water which wasthen sampled by the three different API ion sources.

FIG. 4 shows the relative signal intensities obtained for the five testanalytes with a conventional Electrospray ion source, a conventionalAPCI inn source and an impactor ion source according to the preferredembodiment. For each analyte the signal intensity was monitored for theprotonated molecule ([M+H]⁺). However, owing to signal saturation withthe preferred impactor spray, the cholesterol signal was measured on thecarbon-13 isotope of the [M+H]⁺ ion. From this figure, it is clear thatalthough the APCI ion source has some advantages over ESI ion sources(e.g. for non-polar analytes such as cholesterol), ESI is generally themore sensitive of these two techniques. It is also clear that thepreferred impactor spray source gives rise to significantly greatersignal intensities than either the ESI or APCI ion source for allcompound types.

In API ion sources that utilize the SACI ionization technique, a broadarea target is maintained at an elevated potential to optimize ionsignal. FIG. 5 shows the effect of varying the target potential on theresulting ion signal for the preferred impactor spray source where thesame test mixture was analysed with a target potential of 2.2 kVfollowed by a target potential of 0 kV. In contrast to SACI, it isapparent that an elevated target potential, although advantageous, isnot essential to the ionization process. By contrast, a broad area SACIsource would lose >90% of the ion signal under the same experimentalconditions (data not shown).

Although not essential, an elevated target potential is nonethelessadvantageous and has the result of improving the qualitative aspects ofmass spectral data. To illustrate this, FIG. 6A shows a mass spectrumobtained from an impactor ion source according to the preferredembodiment with a target potential of 2.2 kV, FIG. 6B shows a massspectrum obtained from an impactor ion source according to an embodimentwith a target potential of 0V and FIG. 6C shows a mass spectrum obtainedwith a conventional electrospray source with an optimized capillarypotential of 4 kV. The mass spectra shown in FIGS. 6A and 6B which wereobtained using an ion source according to the preferred embodiment areshown to produce more analyte ions than ESI but significantly anelevated target potential also reduces the susceptibility to ion adductformation ([M+Na]⁺ and [M+K]⁺) such that the protonated molecule([M+H]⁺) is the base peak only for the mass spectrum shown in FIG. 6A.

An experiment was conducted to compare the sensitivity of the impactorion source according to the preferred embodiment with a SACI-typeionization source. FIG. 7 shows a schematic of the SACI ion source whichwas used. The SACI ion source was constructed by replacing the impactorpin target 10 with a 0.15 mm thick rectangular tin sheet 19 whichmeasured approximately 30 mm×15 mm. The sheet target 19 was angled atapproximately 30° to horizontal and was positioned such that the pointof intersection between the nebuliser or probe 2 axis and the target 19was at X=4 min and Z=4 mm. The SACI ion source was optimised at anebuliser or sprayer potential of 0 V and a target potential of 1 kV.All other gas flows and voltages were as described for the preferredimpactor spray source.

FIG. 8 compares the relative signal intensities obtained with a SACI ionsource and an impactor ion source according to the preferred embodiment.It is observed that the preferred impactor spray ion source is typicallybetween ×5-10 more sensitive than the broad area SACI ion source.

Further embodiments are contemplated wherein the performance of thepreferred impactor ion source may be further improved by positioning acentral wire in the bore of the liquid capillary tube 3. Videophotography has shown that the central wire focuses the droplet streamsuch that the target may be placed at the focal point to furtherincrease the droplet flux density. The position of the focal point iscomparable to the sprayer tip/target distance used in the preferredembodiment (1-2 mm).

As described above a SACI ion source converts a liquid stream into avapour stream that then impinges on a broad area target. Experiments onSACI (Cristoni et al., J. Mass Spectrom., 2005, 40, 1550) have shownthat ionisation occurs as a result of the interaction, of neutralanalyte molecules in the gas phase with the proton rich surface of thebroad area target. Furthermore, there is a linear relationship betweenionisation efficiency and target area within the range 1-4 cm².

In contrast to SACI, the preferred ion source uses a streamlined targetto intercept a high velocity stream of liquid droplets which results ina secondary stream consisting of secondary droplets, gas phase neutralsand ions.

A pneumatic nebuliser according to an embodiment of the presentinvention was investigated further. The nebuliser comprised an innerliquid capillary with an internal diameter of 127 μm and an outerdiameter of 230 μm. The inner liquid capillary was surrounded by a gascapillary with an internal diameter of 330 μm that was pressurised to 7bar.

FIG. 9 shows typical data obtained from a Phase Doppler Anemometry(“PDA”) analysis of the preferred nebuliser for a 1 mL/min liquid flowconsisting of 90% water/10% methanol and a nitrogen nebuliser gas.

The PDA sampling point was scanned radially across the spray (probeaxis=0) at an axial distance of 5 mm from the spray point i.e.equivalent to the typical nebuliser/target distance according to thepreferred embodiment. FIG. 9 shows that the nebuliser typically producesliquid droplets with a Sauter mean diameter (d₃₂) in the range 13-20 μmwith mean axial velocities in excess of 100 ms⁻¹.

FIG. 9 also shows that the very high velocity droplets are wellcollimated and are typically confined within a radius of 1 mm from theprobe axis.

The upper trace of FIG. 10 shows the radial distribution of the datarate N/T (number of validated samples per unit time) for the preferredpneumatic nebuliser and experimental conditions as described above. Thislogrithmic plot demonstrates that the spray is well collimated withgreater than two thirds of the total droplet mass being confined to aradius of 1 mm from the probe axis. The lower trace of FIG. 10 shows theequivalent N/T distribution from a heated nebuliser such as used in aconventional SACI source. The heated nebuliser consists of a pneumaticnebuliser which sprays into a 90 mm long cylindrical tube with a 4 mmdiameter bore (tube temperature=600° C.). The N/T data for thisnebuliser was obtained at an axial distance of 7 mm from the exit end ofthe heated tube. It is important to note that the N/Ts for the fewdetected droplets from the heated nebuliser (d₃₂ was typically 14 μm,data not shown) are typically three orders of magnitude lower than thoseobtained from the pneumatic nebuliser according to the preferredembodiment. This is a due to the fact that the overwhelming mass of theliquid is vaporised in the SACI-type heated nebuliser resulting in astream of vapour that contains a very low number density of survivingdroplets.

Accordingly, a known SACI ion source should be construed as comprising anebuliser which emits a stream predominantly of vapour and hence a SACIion source should be understood as not falling within the scope of thepresent invention.

Referring to the data presented in FIGS. 9 and 10 it can be assumed thatthe physical model of the ion source according to the preferredembodiment is dominated by the impact of high velocity liquid dropletson a target that is indirectly heated by the source heater. Such impacteffects give rise to the formation of secondary droplets, where thenature of the droplet breakup is determined by the Weber number W_(e)which is given by the following:W _(e) =ρU ² d/σ  (1)wherein ρ is the droplet density, U is the droplet velocity, d is thedroplet diameter and σ is the droplet surface tension.

If it is assumed that the water droplets are at 40° C., the nitrogen gasenviroment is at 100° C., d=18 μm and U=50 ms⁻¹ then a value ofW_(e)=640 is obtained for the droplets according to the preferredembodiment. It has been shown (in the literature) that the number ofreatomised water droplets increases linearly with W_(e) in the range50-750 for impact on a heated steel target for temperatures between260-400° C. At W_(e)=750, a single droplet typically gave rise to 40secondary droplets.

It is apparent, therefore, that the impactor target leads to significantdroplet breakup to produce a secondary stream that consists of chargeddroplets, neutrals, ions and clusters.

The impact efficiency of the system will be largely governed by theStokes number S_(k) where:S _(k) =ρd ² U/18μa  (2)wherein ρ is the droplet density, d is the droplet diameter, U is thedroplet velocity, μ is the gas viscosity and a is the characteristicdimension of the target.

Impact efficiency increases with increasing S_(k) and thus favours largedroplets with high velocity and a small target diameter. Thus for thepreferred impactor spray conditions described above, it may may beexpected that S_(k) has a typical value of 30.

For S_(k)>>1 droplets are highly likely to deviate from the flowstreamlines and impact upon the target. In contrast, if the targetdimension is increased by an order of magnitude and the velocity isdecreased by an order of magnitude (i.e. similar conditions to SACI),then the value of S_(k) drops to 0.3 at which point the droplets aremore likely to follow the gas flow around the target. The impactefficiency is also known to increase with reducing Reynolds numberswhich will further favour the streamlined nature of the impactor spraytarget according to the preferred embodiment.

The shape of the secondary stream will be governed by the gas flowdynamics and, in particular, the Reynolds number (R_(e)) which is givenby:R _(e) =ρvL/μ  (3)wherein ρ is the gas density, v is the gas velocity, μ is the gasviscosity and L is the significant dimension of the target.

With a 1 mm diameter impactor target, a gas velocity of 50 ms⁻¹ andnitrogen gas at 100° C. then a value of R_(e)=3000 is obtained.

Reynolds numbers in the range 2000-3000 generally correspond to thetransition region from laminar to turbulent flow. Therefore, it can beexpected that the wake from the target contains some turbulence and eddyfeatures, However, severe turbulence that could hinder the sampling ofions or droplets at the ion inlet cone is not expected.

The preferred ion source can be tuned by swinging the nebuliser to movethe impact zone from one side of the rod-like target to the other. Thisresults in changes to the wake which can be visually observed by strongillumination of the secondary droplet stream. Other embodiments aretherefore also contemplated wherein similar source optimisation could beachieved with a centralised impact zone and a non-symmetric target crosssection e.g. (the profile of) an aircraft wing.

Although the present invention has been described with reference topreferred embodiments it will be apparent to those skilled in the artthat various changes in form and detail may be made without departingfrom the scope of the invention as defined by the accompanying claims.

The invention claimed is:
 1. An ion source comprising: one or morenebulisers and one or more targets; wherein said one or more nebulisersare arranged and adapted to nebulise one or more eluents emitted by oneor more liquid chromatography separation devices over a period of time;wherein said one or more eluents have a liquid flow rate selected fromthe group consisting of: (i) 1-10 μL/min; (ii) 10-50 μL/min; (iii)50-100 μL/min; (iv) 100-200 μL/min; (v) 200-300 μL/min; (vi) 300-400μL/min; (vii) 400-500 μL/min; (viii) 500-600 μL/min; (ix) 600-700μL/min; (x) 700-800 μL/min; (xi) 800-900 (xii) 900-1000 μL/min; (xiii)1000-1500 μL/min; (xiv) 1500-2000 μL/min; (xv) 2000-2500 μL/min; and(xvi) >2500 μL/min; wherein said one or more nebulisers are arranged andadapted to emit, in use, a stream predominantly of droplets which arecaused to impact upon said one or more targets and to ionise saiddroplets to form a plurality of ions; wherein a mean axial impactvelocity of said droplets upon said one or more targets is ≧20 m/s; andwherein said one or more targets are arranged <10 mm from an exit ofsaid one or more nebulisers.
 2. An ion source as claimed in claim 1,wherein said droplets comprise analyte droplets and said plurality ofions comprise analyte ions.
 3. An ion source as claimed in claim 1,wherein said droplets comprise reagent droplets and said plurality ofions comprise reagent ions.
 4. An ion source as claimed in claim 3,further comprising one or more tubes arranged and adapted to supply oneor more analyte or other gases to a region adjacent said one or moretargets.
 5. An ion source as claimed in claim 4, wherein said reagentions are arranged so as to ionise said analyte gas to form a pluralityof analyte ions.
 6. An ion source as claimed in claim 3, wherein saidone or more targets are coated with one or more liquid, solid orgelatinous analytes and wherein said one or more analytes are ionised toform a plurality of analyte ions.
 7. An ion source as claimed in claim3, wherein said one or more targets are formed from one or more analytesand wherein said one or more analytes are ionised to form a plurality ofanalyte ions.
 8. An ion source as claimed in claim 1, wherein an analyteliquid is supplied to said one or more targets and is ionised to form aplurality of analyte ions or a reagent liquid is supplied to said one ormore targets and is ionised to form reagent ions which transfer chargeto neutral analyte atoms or molecules to form analyte ions or whichenhance the formation of analyte ions.
 9. An ion source as claimed inclaim 8, wherein said one or more targets comprise one or more aperturesand wherein said analyte liquid or said reagent liquid is supplieddirectly to said one or more targets and emerges from said one or moreapertures.
 10. An ion source as claimed in claim 1, wherein said ionsource comprises an Atmospheric Pressure Ionisation (“API”) ion source.11. An ion source as claimed in claim 1, wherein said one or morenebulisers are arranged and adapted such that a majority of mass ormatter emitted by said one or more nebulisers is formed of droplets notvapour.
 12. An ion source as claimed in claim 11, wherein at least 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of mass or matter emittedby said one or more nebulisers is formed of droplets.
 13. An ion sourceas claimed in claim 1, wherein said one or more nebulisers are arrangedand adapted to emit a stream of droplets wherein a Sauter mean diameter(“SMD”, d32) of said droplets is in a range: (i) <5 μm; (ii) 5-10 μm;(iii) 10-15 μm; (iv) 15-20 μm; (v) 20-25 μm; or (vi) >25 μm.
 14. An ionsource as claimed in claim 1, wherein said stream of droplets emittedfrom said one or more nebulisers forms a stream of secondary dropletsafter impacting said one or more targets.
 15. An ion source as claimedin claim 14, wherein said stream of droplets or said stream of secondarydroplets traverse a flow region with a Reynolds number (Re) in a rangeof: (i) <2000; (ii) 2000-2500; (iii) 2500-3000; (iv) 3000-3500; (v)3500-4000; or (vi) >4000.
 16. An ion source as claimed in claim 1,wherein when said droplets impact said one or more targets said dropletshave a Weber number (We) selected from the group consisting of: (i) <50;(ii) 50-100; (iii) 100-150; (iv) 150-200; (v) 200-250; (vi) 250-300;(vii) 300-350; (viii) 350-400; (ix) 400-450; (x) 450-500; (xi) 500-550;(xii) 550-600; (xiii) 600-650; (xiv) 650-700; (xv) 700-750; (xvi)750-800; (xvii) 800-850; (xviii) 850-900; (xix) 900-950; (xx) 950-1000;and (xxi) >1000.
 17. An ion source as claimed in claim 1, wherein whensaid droplets impact said one or more targets said droplets have aStokes number (S_(k)) in the range: (i) 1-5; (ii) 5-10; (iii) 10-15;(iv) 15-20; (v) 20-25; (vi) 25-30; (vii) 30-35; (viii) 35-40; (ix)40-45; (x) 45-50; and (xi) >50.
 18. An ion source as claimed in claim 1,wherein a mean axial impact velocity of said droplets upon said one ormore targets is selected from the group consisting of (i) 20-30 m/s;(ii) 30-40 m/s; (iii) 40-50 m/s; (iv) 50-60 m/s; (v) 60-70 m/s; (vi)70-80 m/s; (vii) 80-90 m/s; (viii) 90-100 m/s; (ix) 100-110 m/s; (x)110-120 m/s; (xi) 120-130 m/s; (xii) 130-140 m/s; (xiii) 140-150 m/s;and (xiv) >150 m/s.
 19. An ion source as claimed in claim 1, whereinsaid one or more targets are arranged <9 min, <8 mm, <7 mm, <6 mm, <5mm, <4 mm, <3 mm or <2 mm from an exit of said one or more nebulisers.20. An ion source as claimed in claim 1, wherein said one or morenebulisers comprises a first capillary tube having an exit which emits,in use, said stream of droplets.
 21. An ion source as claimed in claim20, wherein said first capillary tube is maintained, in use, at apotential: (i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv) −2to −1 kV; (v) −1000 to −900 V; (vi) −900 to −800 V; (vii) −800 to −700V; (viii) −700 to −600 V; (ix) −600 to −500 V; (x) −500 to −400 V; (xi)−400 to −300 V; (xii) −300 to −200 V; (xiii) −200 to −100 V; (xiv) −100to −90 V; (xv) −90 to −80 V; (xvi) −80 to −70 V; (xvii) −70 to −60 V;(xviii) −60 to −50 V; (xix) −50 to −40 V; (xx) −40 to −30 V; (xxi) −30to −20 V; (xxii) −20 to −10 V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv)10-20 V; (xxvi) 20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V; (xxix) 50-60V; (xxx) 60-70 V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V;(xxxiv) 100-200 V; (xxxv) 200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500V; (xxxviii) 500-600 V; (xxxix) 600-700 V; (xl) 700-800 V; (xli) 800-900V; (xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV; (xlv) 3-4 kV; and(xlvi) 4-5 kV.
 22. An ion source as claimed in claim 20, wherein saidfirst capillary tube is maintained, in use, at a potential of: (i) −5 to−4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv) −2 to −1 kV; (v) −1000to −900 V; (vi) −900 to −800 V; (vii) −800 to −700 V; (viii) −700 to−600 V; (ix) −600 to −500 V; (x) −500 to −400 V; (xi) −400 to −300 V;(xii) −300 to −200V; (xiii) −200 to −100 V; (xiv) −100 to −90 V; (xv)−90 to −80 V; (xvi) −80 to −70 V; (xvii) −70 to −60 V; (xviii) −60 to−50 V; (xix) −50 to −40 V; (xx) −40 to −30 V; (xxi) −30 to −20 V; (xxii)−20 to −10 V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv) 10-20 V; (xxvi)20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V; (xxix) 50-60 V; (xxx) 60-70V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V; (xxxiv) 100-200V; (xxxv) 200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500 V; (xxxviii)500-600 V; (xxxix) 600-700 V; (xl) 700-800 V; (xli) 800-900 V; (xlii)900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV; (xlv) 3-4 kV; and (xlvi) 4-5kV; relative to the potential of an enclosure surrounding said ionsource or an ion inlet device which leads to a first vacuum stage of amass spectrometer or said one or more targets.
 23. An ion source asclaimed in claim 20, further comprising a wire located within a volumeenclosed by said first capillary tube wherein said wire is arranged andadapted to focus said stream of droplets.
 24. An ion source as claimedin claim 20, wherein either: (i) said first capillary tube is surroundedby a second capillary tube which is arranged and adapted to provide astream of gas to the exit of said first capillary tube; or (ii) a secondcapillary tube is arranged and adapted to provide a cross flow stream ofgas to the exit of said first capillary tube.
 25. An ion source asclaimed in claim 24, wherein said second capillary tube surrounds saidfirst capillary tube or is either concentric or non-concentric with saidfirst capillary tube.
 26. An ion source as claimed in claim 24, whereinends of said first and second capillary tubes are either: (i) flush orparallel with each other; or (ii) protruded, recessed or non-parallelrelative to each other.
 27. An ion source as claimed in claim 20,wherein the exit of said first capillary tube has a diameter D and saidstream of droplets is arranged to impact on an impact zone of said oneor more targets.
 28. An ion source as claimed in claim 27, wherein saidimpact zone has a maximum dimension of x and wherein the ratio x/D is≦30.
 29. An ion source as claimed in claim 27, wherein said impact zonehas an area selected from the group consisting of: (i) <0.01 mm²; (ii)0.01-0.10 mm²; (iii) 0.10-0.20 mm²; (iv) 0.20-0.30 mm²; (v) 0.30-0.40mm²; (vi) 0.40-0.50 mm²; (vii) 0.50-0.60 mm²; (viii) 0.60-0.70 mm²; (ix)0.70-0.80 mm²; (x) 0.80-0.90 mm²; (xi) 0.90-1.00 mm²; (xii) 1.00-1.10mm²; (xiii) 1.10-1.20 mm²; (xiv) 1.20-1.30 mm²; (xv) 1.30-1.40 mm²;(xvi) 1.40-1.50 mm²; (xvii) 1.50-1.60 mm²; (xviii) 1.60-1.70 mm²; (xix)1.70-1.80 mm²; (xx) 1.80-1.90 mm²; (xxi) 1.90-2.00 mm²; (xxii) 2.00-2.10mm²; (xxiii) 2.10-2.20 mm²; (xxiv) 2.20-2.30 mm²; (xxv) 2.30-2.40 mm²;(xxvi) 2.40-2.50 mm²; (xxvii) 2.50-2.60 mm²; (xxviii) 2.60-2.70 mm²;(xxix) 2.70-2.80 mm²; (xxx) 2.80-2.90 mm²; (xxxi) 2.90-3.00 mm²; (xxxii)3.00-3.10 mm²; (xxxiii) 3.10-3.20 mm²; (xxxiv) 3.20-3.30 mm²; (xxxv)3.30-3.40 mm²; (xxxvi) 3.40-3.50 mm²; (xxxvii) 3.50-3.60 mm²; (xxxviii)3.60-3.70 mm²; (xxxix) 3.70-3.80 mm²; (xl) 3.80-3.90 mm²; and (xli)3.90-4.00 mm².
 30. An ion source as claimed in claim 1, furthercomprising one or more heaters which are arranged and adapted to supplyone or more heated streams of gas to the exit of said one or morenebulisers.
 31. An ion source as claimed in claim 30, wherein either:(i) said one or more heaters surround said first capillary tube and arearranged and adapted to supply a heated stream of gas to the exit ofsaid first capillary tube; or (ii) said one or more heaters comprise oneor more infra-red heaters; or (iii) said one or more heaters compriseone or more combustion heaters.
 32. An ion source as claimed in claim 1,further comprising one or more heating devices arranged and adapted todirectly or indirectly heat said one or more targets.
 33. An ion sourceas claimed in claim 32, wherein said one or more heating devicescomprise one or more lasers arranged and adapted to emit one or morelaser beams which impinge upon said one or more targets in order to heatsaid one or more targets.
 34. An ion source as claimed in claim 1,wherein said one or more targets are maintained, in use, at a potential:(i) −5 to −4 kV; (ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv) −2 to −1 kV;(v) −1000 to −900 V; (vi) −900 to −800 V; (vii) −800 to −700 V; (viii)−700 to −600 V; (ix) −600 to −500 V; (x) −500 to −400 V; (xi) −400 to−300 V; (xii) −300 to −200 V; (xiii) 200 to −100 V; (xiv) −100 to −90 V;(xv) −90 to −80 V; (xvi) −80 to −70 V; (xvii) −70 to −60 V; (xviii) −60to −50 V; (xix) −50 to −40 V; (xx) −40 to −30 V; (xxi) −30 to −20 V;(xxii) −20 to −10 V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv) 10-20 V;(xxvi) 20-30 V; (xxvii) 30-40V; (xxviii) 40-50 V; (xxix) 50-60 V; (xxx)60-70 V; (xxxi) 70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V; (xxxiv)100-200 V; (xxxv) 200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500 V;(xxxviii) 500-600 V; (xxxix) 600-700 V; (xi) 700-800 V; (xli) 800-900 V;(xlii) 900-1000 V; (xliii) 1-2 kV; (xliv) 2-3 kV; (xiv) 3-4 kV; and(xlvi) 4-5 kV.
 35. An ion source as claimed in claim 1, wherein said oneor more targets are maintained, in use, at a potential (i) −5 to −4 kV;(ii) −4 to −3 kV; (iii) −3 to −2 kV; (iv) −2 to −1 kV; (v) −1000 to −900V; (vi) −900 to −800 V; (vii) −800 to −700 V; (viii) −700 to −600 V;(ix) −600 to −500 V; (x) −500 to −400 V; (xi) −400 to −300 V; (xii) −300to −200 V; (xiii) −200 to −100 V; (xiv) −100 to −90 V; (xv) −90 to −80V; (xvi) −80 to −70 V; (xvii) −70 to −60 V; (xviii) −60 to −50 V; (xix)−50 to −40 V; (xx) −40 to −30 V; (xxi) −30 to −20 V; (xxii) −20 to −10V; (xxiii) −10 to 0V; (xxiv) 0-10 V; (xxv) 10-20 V; (xxvi) 20-30 V;(xxvii) 30-40V; (xxviii) 40-50 V; (xxix) 50-60 V; (xxx) 60-70 V; (xxxi)70-80 V; (xxxii) 80-90 V; (xxxiii) 90-100 V; (xxxiv) 100-200 V; (xxxv)200-300 V; (xxxvi) 300-400 V; (xxxvii) 400-500 V; (xxxviii) 500-600 V;(xxxix) 600-700 V; (xi) 700-800 V; (xli) 800-900 V; (xlii) 900-1000 V;(xliii) 1-2 kV; (xliv) 2-3 kV; (xlv) 3-4 kV; and (xlvi) 4-5 kV; relativeto the potential of an enclosure surrounding said ion source or an ioninlet device which leads to a first vacuum stage of a mass spectrometeror said one or more nebulisers.
 36. An ion source as claimed in claim 1,wherein in a mode of operation said one or more targets are maintainedat a positive potential and wherein said droplets impacting upon saidone or more targets form a plurality of positively charged ions.
 37. Anion source as claimed in claim 1, wherein in a mode of operation saidone or more targets are maintained at a negative potential and whereinsaid droplets impacting upon said one or more targets form a pluralityof negatively charged ions.
 38. An ion source as claimed in claim 1,further comprising a device arranged and adapted to apply a sinusoidalor non-sinusoidal AC or RF voltage to said one or more targets.
 39. Anion source as claimed in claim 1, wherein said one or more targets arearranged or otherwise positioned so as to deflect said stream ofdroplets or said plurality of ions towards an ion inlet device of a massspectrometer.
 40. An ion source as claimed in claim 1, wherein said oneor more targets are positioned upstream of an ion inlet device of a massspectrometer so that ions are deflected towards said ion inlet device.41. An ion source as claimed in claim 1, wherein said one or moretargets comprise a stainless steel target, a metal, gold, a non-metallicsubstance, a semiconductor, a metal or other substance with a carbidecoating, an insulator or a ceramic.
 42. An ion source as claimed inclaim 1, wherein said one or more targets comprise a plurality of targetelements so that droplets from said one or more nebulisers cascade upona plurality of target elements or wherein said target is arranged tohave multiple impact points so that droplets are ionised by multipleglancing deflections.
 43. An ion source as claimed in claim 1, whereinsaid one or more targets are shaped so that gas flowing past said one ormore targets is directed or deflected towards, parallel to, orthogonalto or away from an ion inlet device of a mass spectrometer.
 44. An ionsource as claimed in claim 43, wherein at least some or a majority ofsaid plurality of ions are arranged so as to become entrained, in use,in said gas flowing past said one or more targets.
 45. An ion source asclaimed in claim 1, wherein in a mode of operation droplets from one ormore reference or calibrant nebulisers are directed onto said one ormore targets.
 46. An ion source as claimed in claim 1, wherein in a modeof operation droplets from one or more analyte nebulisers are directedonto said one or more targets.
 47. A mass spectrometer comprising an ionsource as claimed in claim
 1. 48. A mass spectrometer as claimed inclaim 47, further comprising an ion inlet device which leads to a firstvacuum stage of said mass spectrometer.
 49. A mass spectrometer asclaimed in claim 48, wherein said ion inlet device comprises an ionorifice, an ion inlet cone, an ion inlet capillary, an ion inlet heatedcapillary, an ion tunnel, an ion mobility spectrometer or separator, adifferential ion mobility spectrometer, a Field Asymmetric Ion MobilitySpectrometer (“FAIMS”) device or other ion inlet.
 50. A massspectrometer as claimed in claim 49, wherein the one or more targetscomprise either one or more rods or one or more pins having a tapercone, said stream of droplets is arranged to impact said one or morerods or said taper cone of said one or more pins either: (i) directly ona centerline of said one or more rods or pins; or (ii) on a side of saidone or more rods or said taper cone of said one or more pins which facestowards or away from said ion orifice.
 51. A mass spectrometer asclaimed in claim 48, wherein said one or more targets are located at afirst distance X₁ in a first direction from said ion inlet device and ata second distance Z₁ in a second direction from said ion inlet device,wherein said second direction is orthogonal to said first direction andwherein: (i) X₁ is selected from the group consisting of: (i) 0-1 mm;(ii) 1-2 mm; (iii) 2-3 mm; (iv) 3-4 mm; (v) 4-5 mm; (vi) 5-6 mm; (vii)6-7 mm; (viii) 7-8 mm; (ix) 8-9 mm; (x) 9-10 mm; and (xi) >10 mm; or(ii) Z₁ is selected from the group consisting of (i) 0-1 mm; (ii) 1-2mm; (iii) 2-3 mm; (iv) 3-4 mm; (v) 4-5 mm; (vi) 5-6 mm; (vii) 6-7 mm;(viii) 7-8 mm; (ix) 8-9 mm; (x) 9-10 mm; and (xi) >10 mm.
 52. A massspectrometer as claimed in claim 48, wherein said one or more targetsare positioned so as to deflect said stream of droplets or saidplurality of ions towards said ion inlet device.
 53. A mass spectrometeras claimed in claim 48, wherein said one or more targets are positionedupstream of said ion inlet device.
 54. A mass spectrometer as claimed inclaim 48, further comprising an enclosure enclosing said one or morenebulisers, said one or more targets and said ion inlet device.
 55. Amass spectrometer as claimed in claim 48, further comprising one or moredeflection or pusher electrodes, wherein in use one or more DC voltagesor DC voltage pulses are applied to said one or more deflection orpusher electrodes in order to deflect or urge ions towards an ion inletdevice of said mass spectrometer.
 56. A method of ionising a samplecomprising: nebulising one of more eluents emitted by one or more liquidchromatography separation devices over a period of time; wherein saidone or more eluents have a liquid flow rate selected from the groupconsisting of: (i) 1-10 μL/min; (ii) 10-50 μL/min; (iii) 50-100 μL/min;(iv) 100-200 μL/min; (v) 200-300 (vi) 300-400 μL/min; (vii) 400-500μL/min; (viii) 500-600 μL/min; (ix) 600-700 μL/min; (x) 700-800 μL/min;(xi) 800-900 μL/min; (xii) 900-1000 μL/min; (xiii) 1000-1500 μL/min;(xiv) 1500-2000 μL/min; (xv) 2000-2500 μL/min; and (xvi) >2500 μL/min;causing a stream predominantly of droplets to impact upon one or moretargets to ionise said droplets to form a plurality of analyte ions;wherein a mean axial impact velocity of said droplets upon said one ormore targets is ≧20 m/s; and wherein said stream is emitted by one ormore nebulisers and wherein said one or more targets are arranged <10 mmfrom an exit of said one or more nebulisers.
 57. A method of massspectrometry comprising a method of ionising a sample as claimed inclaim 56.